SFEBES2012 Poster Presentations Obesity, diabetes, metabolism and cardiovascular (73 abstracts)
Investigating the sites and mechanisms by which peripheral prokineticin 2 administration reduces food intake and body weight in mice
Kylie Beale 1 , James Gardiner 1 , Gavin Bewick 1 , Klara Hostomska 1 , Neekhil Patel 1 , Syed Hussain 1 , Francis Ebling 2 , Preeti Jethwa 2 , Haydn Prosser 3 , Mohammad Ghatei 1 , Stephen Bloom 1 & Waljit Dhillo 1
1Investigative Medicine, Imperial College London, London, United Kingdom; 2School of Biomedical Sciences, University of Nottingham Medical School, Nottingham, United Kingdom; 3The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom.
Prokineticin 2 (PK2) is a neuropeptide expressed in hypothalamic nuclei involved in the regulation of energy homeostasis, and has been shown to acutely reduce food intake in rodents. PK2 binds to and activates two G protein-coupled receptors, the PK receptor 1 (PKR1) and the PK receptor 2 (PKR2). We aimed to determine the sites and receptors which mediate the anorectic effects of peripherally administered PK2 within the CNS. We investigated neuronal activity in the hypothalamus and brainstem following intra-peritoneal (IP) administration of PK2 using c-Fos-like immunoreactivity (CFL-IR). The anorectic effect of PK2 was compared in wild type and prokineticin receptor 2 (PKR2) knockout mice. Finally, diet-induced obese mice were implanted with an osmotic mini-pump containing saline or PK2 (60 or 120 nmol/kg/hr). Body weight and food intake were monitored for 14 days. At the termination of the study, brainstem were dissected and analysed for mRNA expression of neuropeptides known to regulate energy homeostasis. IP PK2 administration significantly increased CFL-IR in the dorsal motor vagal nucleus of the brainstem. No activation was observed in the hypothalamus. The anorectic effect of PK2 was maintained in mice lacking the PKR2, suggesting that the PKR1 may mediate the effect of PK2 on feeding. Chronic, peripheral administration of PK2 significantly reduced body weight and food intake compared to saline controls. No significant difference in the expression of pro-opiomelanocortin mRNA was seen in PK2-treated mice compared to saline controls. Our data suggests that the anorectic effects of PK2 are mediated via the brainstem, and that this effect does not require the PKR2. Chronic administration of PK2 significantly reduced food intake and body weight in obese mice, although the downstream pathways underlying this effect require further investigation.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: Declaration of Funding: The Section is funded by grants from the MRC, BBSRC, NIHR, an Integrative Mammalian Biology (IMB) Capacity Building Award, an FP7- HEALTH- 2009- 241592 EurOCHIP grant and is supported by the NIHR Imperial Biomedical Research Centre Funding Scheme. This work was was partly funded by an academic grant from Astra Zeneca.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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